Lymph nodes & spleen, nonlymphoma
Lymph nodes-inflammatory / reactive disorders
Drug hypersensitivity
Author: Jayalakshmi Balakrishna, M.D.
Editorial Board Member: Genevieve M. Crane, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 1 March 2018
Last staff update: 12 May 2021
Copyright: 2003-2024, PathologyOutlines.com, Inc.
PubMed Search: "Drug hypersensitivity" lymph nodes[mh]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Flow cytometry description | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Balakrishna J. Drug hypersensitivity. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesdrughypersensitivity.html. Accessed December 18th, 2024.
Definition / general
- Certain drugs may give rise to soft lymph node enlargement, predominantly in the neck (J Pathol Bacteriol 1968;95:314)
- Lymphadenopathy may occur alone or be associated with involvement of other organs (Neurology 1979;29:1480)
- May resemble lymphoma by morphology
- When the drug is stopped, the lymphadenopathy usually disappears in 1 - 2 weeks
- Can present with lymphadenopathy or with a rare systemic disorder, DIHS / DRESS (Drug Induced Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms (Rev Assoc Med Bras 2016;62:227)
Essential features
- History of drug exposure
- Polymorphous infiltrate composed of immunoblasts, small lymphocytes, plasma cells, eosinophils and histiocytes
Terminology
- Drug induced lymphadenopathy
- Hydantoin lymphadenopathy
- Pseudolymphoma syndrome
- Drug induced hypersensitivity syndrome (DIHS)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
ICD coding
Epidemiology
- Uncommon
- Pediatric population
Sites
- Predominantly cervical but all lymph node groups can be affected
- Can be generalized
Pathophysiology
- Different theories have been proposed:
- Hapten: drug molecules become antigenic when bound to a carrier protein, creating an immune response (Curr Opin Immunol 2012;24:730)
- p-i concept: direct binding of drugs and their metabolites to HLA trigger T cell responses (Curr Opin Allergy Clin Immunol 2002;2:301)
- Very strong link between HLA-B*5701 in HIV positive Caucasians and the development of hypersensitivity to abacavir
- Abacavir binds noncovalently and specifically to the peptide binding groove of HLA-B*5701 molecule (Nature 2012;486:554)
- Susceptibility to carbamazepine reactions in patients with HLA-B*1502 variant (Nature 2004;428:486)
- Drug reaction with eosinophilia and systemic symptoms (DRESS) is associated with reactivation of inactive Herpesviridae family viruses, including human herpesvirus 6 (HHV6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) (Arch Dermatol 2001;137:301, Br J Dermatol 2006;155:344, Arch Dermatol 2009;145:1030)
Etiology
- Reaction to drug exposure, including (Am J Med 2011;124:588):
- Abacavir, allopurinol, antibiotics, carbamazepine, dapsone
- Lamotrigine, mexiletine, minocycline, nevirapine
- Oxcarbazepine, phenobarbital, phenytoin (J Pathol Bacteriol 1968;95:314, Neurology 1979;29:1480), salazosulfapyridine
- Sulfamethoxazole, sulfasalazine, strontium ranelate, vancomycin
Clinical features
- Isolated lymph node enlargement OR
- Drug Induced Hypersensitivity Syndrome (DIHS) / Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (Allergol Int 2016;65:432):
- Fever, lymphadenopathy, facial edema, periorbital edema, conjunctival injection
- Abdominal pain, diarrhea, hepatomegaly, splenomegaly
- Skin rash (maculopapular rash, bullous, wheal and flare, plaque, patch, target lesion)
- Internal organ involvement (liver - elevated alanine aminotransferase levels, kidney, lung); also brain (Turk J Pediatr 2015;57:541), heart, muscle, pancreas, thyroid (Int J Mol Sci 2017 Jun 9;18(6) pii: E1243)
- Hematologic abnormalities (eosinophilia, atypical lymphocytes, lymphocytosis, lymphopenia, thrombocytopenia)
Diagnosis
- Clinical history of drug exposure
- Characteristic clinical and laboratory features
- Biopsy of the affected lymph node (rarely done, not required for diagnosis)
Radiology description
- Enlarged lymph nodes
Prognostic factors
- Underlying disease conditions
- Extent of drug exposure
- Drug reaction with eosinophilia and systemic symptoms (DRESS) has 4% mortality (Acta Derm Venereol 2012;92:200)
Case reports
- 17 year old girl presenting with bilateral cervical neck lymphadenopathy (Int J Pediatr Otorhinolaryngol 2017;98:82)
- 20 year old woman with fever of 38°C, prostration and drowsiness (Rev Assoc Med Bras 2016;62:227)
- 24 year old woman with lamotrigine cervical pseudolymphoma (Epilepsy Behav Case Rep 2017;7:40)
- 37 year old woman with redness and edema of inguinal area (Drug Saf Case Rep 2017;4:1)
- 60 year old man with skin rash, fever, distended abdomen and severe pruritus for 10 days (Iran Red Crescent Med J 2016;18:e36825)
Treatment
- Discontinuation of the offending drug
- For severe cases, immunosuppressive drugs / corticosteroids, IV Ig, plasma exchange
Gross description
- Enlarged lymph nodes
Microscopic (histologic) description
- Polymorphous cellular infiltrate composed of lymphocytes, plasma cells, eosinophils and histiocytes, most often with architectural distortion
- Focal hemorrhagic necrosis is usually seen without fibrosis or scarring
- Typical multinucleated Reed-Sternberg cells are absent; however, cells resembling Hodgkin / Reed-Sternberg (HRS) cells may be seen
- Blood vessels show endothelial hyperplasia
- There is variable follicular and paracortical hyperplasia (Hum Pathol 1974;5:519)
Flow cytometry description
- No aberrant immunophenotype
Molecular / cytogenetics description
- No clonal cell populations
Differential diagnosis
- For drug reaction with eosinophilia and systemic symptoms (DRESS) (Rev Assoc Med Bras 2016;62:227):
- Hypereosinophilic syndrome: manifests with urticaria and angioedema and can be a hematopoietic malignancy
- Kawasaki disease: presents with mucosal congestion and desquamation of extremities / skin and lacks eosinophilia and atypical lymphocytes
- Stevens-Johnson syndrome / toxic epidermal necrolysis: lacks eosinophilia, atypical lymphocytosis and lymphadenopathy
- On lymph node biopsy (Hum Pathol 1974;5:519):
- Angioimmunoblastic T cell lymphoma (AITL):
- Presence of vascular proliferation, immunoblasts and polymorphous infiltrate cause confusion with angioimmunoblastic T cell lymphoma
- AITL has characteristic T cells of T follicular helper (TFH) phenotype in perisinusoidal areas and T cell clones, not seen in drug hypersensitivity
- Hodgkin lymphoma:
- Presence of polymorphous inflammatory infiltrate and large Hodgkin / Reed-Sternberg-like cells may cause confusion
- However, classic Hodgkin / Reed-Sternberg cells are not identified in drug hypersensitivity
- Angioimmunoblastic T cell lymphoma (AITL):
Additional references
Board review style question #1
All of the following are proposed pathogenetic mechanisms for drug hypersensitivity, except:
- Direct toxicity
- Drug interactions with specific HLA types
- Hapten theory
- p-i concept
Board review style answer #1
A. Direct toxicity. Drug molecules causing an immune reaction are proposed mechanisms of pathogenesis of drug hypersensitivity, including hapten theory (drug molecules bind to a protein and cause antigenicity), p-i concept (drug molecules bind to HLA and cause T cell response) and drug molecules interacting with certain HLA subtypes. Direct toxicity does not manifest as a drug reaction with eosinophilia and systemic symptoms (DRESS).
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Reference: Drug hypersensitivity
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Reference: Drug hypersensitivity
